{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:18:21Z","timestamp":1791940701877,"version":"4.3.4"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,27]]},"abstract":"<jats:p>Stimulation of endothelial cells by various inflammatory mediators\n leads to release of Weibel\u2013Palade bodies and therefore to exocytosis\n of both P-selectin (adhesion receptor for leukocytes) and von\n Willebrand factor (vWf) (platelet ligand). The potential role of vWf in\n leukocyte recruitment was investigated with the use of vWf-deficient\n mice. We report a strong reduction of leukocyte rolling in venules of\n vWf-deficient mice. Similarly, vWf deficiency led to a decrease in\n neutrophil recruitment in a cytokine-induced meningitis model as well\n as in early skin wounds. In all instances with an antibody that\n preferentially recognizes plasma membrane P-selectin, we observed a\n dramatic reduction in P-selectin expression at the cell surface of\n vWf-deficient endothelium. With confocal microscopy, we found that the\n typical rodlike shape of the Weibel\u2013Palade body is missing in vWf\n \u2212\/\u2212 endothelial cells and that part of the P-selectin content in\n the vWf \u2212\/\u2212 cells colocalized with LAMP-1, a lysosomal marker.\n However, intracellular P-selectin levels were similar in tumor necrosis\n factor \u03b1- and lipopolysaccharide-activated cells of both genotypes.\n We conclude that the absence of vWf, as found in severe von Willebrand\n disease, leads to a defect in Weibel\u2013Palade body formation. This\n defect results in decreased P-selectin translocation to the cell\n surface and reduced leukocyte recruitment in early phases of\n inflammation.<\/jats:p>","DOI":"10.1073\/pnas.061307098","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"4072-4077","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice"],"prefix":"10.1073","volume":"98","author":[{"given":"C\u00e9cile V.","family":"Denis","sequence":"first","affiliation":[{"name":"Center for Blood Research and Department of\r Pathology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Center for Blood Research and Department of\r Pathology, 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